Measurement Of Thyroid Function Research Articles

Association of urinary bisphenols with thyroid function in the general population: a cross-sectional study of an industrial park in China.

Bisphenols (BPs) are potential thyroid disruptors that are widely used in many consumer products, leading to their widespread exposure in the general population. Current cross-sectional and case-control studies have found associations between exposure to BPs and serum thyroid function, but the results were contradictory. The objectives of this study are to describe demographic characteristics, BP exposure levels, and thyroid function measurements in potentially exposed and control districts and to investigate the association of urinary BPs with thyroid function. Data were collected from a general population aged 3-79 years (N = 281) recruited by the Zhejiang Human Biomonitoring Program (ZJHBP). The concentrations of 10 kinds of BPs in urine and serum free triiodothyronine (FT3), total triiodothyronine (TT3), free thyroxine (FT4), total thyroxine (TT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), thyroglobulin antibodies (TgAb), thyroid peroxidase antibodies (TPOAb), and thyrotropin receptor antibody (TRAb) in serum were measured. Multiple linear regression and weighted quantile sum (WQS) regression were used to estimate the relationship between single and mixed exposure of BPs and thyroid function. Bisphenol A (BPA), bisphenol S (BPS), and bisphenol P (BPP) were detected, respectively, in 82.73%, 94.24%, and 55.40% of the population in the exposed area and 81.69%, 61.27%, and 43.66% of the population in the control area. Among adult females, serum TT3 was negatively associated with urinary BPA (β = -0.033, 95% CI = -0.071, -0.008, P = 0.021). Among minor females, FT4 and Tg levels were negatively associated with the urinary BPA (β = -0.026, 95% CI = -0.051, -0.002, P = 0.032 for FT4; β = -0.129, 95% CI = -0.248, -0.009, P = 0.035 for Tg), and TPOAb was positively associated with urinary BPA (β = 0.104, 95% CI = 0.006, 0.203, P = 0.039). In WQS models, BPs mixture was positively associated with FT3 (βWQS = 0.022, 95% CI = 0.002, 0.042) and TT3 (βWQS = 0.033, 95% CI = 0.004, 0.062), and negatively associated with FT4 (βWQS = -0.024, 95% CI = -0.044, 0.004). We found widespread exposure to BPA, BPS, and BPP in the general population of Zhejiang province and found an association between BPA and thyroid hormones. This association is gender- and age-dependent and needs to be confirmed in further studies.

Depression severity partially mediates the association between thyroid function and psychotic symptoms in first-episode, drug-naive major depressive disorder patients with comorbid anxiety at different ages of onset

BackgroundAnxiety and psychotic symptoms are common in patients with major depressive disorder (MDD), with a strong association with thyroid function. Age of onset contributes to the heterogeneity of MDD patients. This study aimed to assess the prevalence of psychotic symptoms in MDD patients with comorbid anxiety and to explore the relationship between thyroid function and psychotic symptoms by ages of onset. MethodsA total of 894 first-episode, drug-naïve Chinese Han MDD patients with comorbid anxiety were recruited. Thyroid function and psychometric measures including Hamilton Anxiety Scale, Hamilton Depression Scale, and Positive and Negative Syndrome Scale were evaluated. Patients were divided into early adulthood onset (EAO, < 45 years old) and mid-adulthood onset (MAO, ≥ 45 years old) groups. ResultsThe MAO subgroup had a higher prevalence of psychotic symptoms compared to EAO subgroup. TSH and TPOAb levels were positively correlated with psychotic symptoms severity, with a more pronounced effect in MAO subgroup. Furthermore, MDD severity partially mediated the effects of TPOAb and TSH levels on psychotic symptoms in both subgroups. LimitationsA causal relationship could not be demonstrated with this cross-sectional study, and the results should be limited to first-episode, drug-naïve MDD patients without considering more potential confounders. Moreover, the male-to-female ratio imbalance is present. ConclusionsOur results indicated that age of onset moderated the association between thyroid function and psychotic symptom, and depression severity partially mediated the effects of thyroid function on psychotic symptoms, suggesting thyroid function may serve as a biomarker of psychotic symptoms in MDD patients with anxiety.

Migraine and thyroid dysfunction: Co-occurrence, shared genes and biological mechanisms.

Migraine and thyroid dysfunction, particularly hypothyroidism, are common medical conditions and are known to have high heritability. Thyroid function measures, thyroid stimulating hormone (TSH) and free thyroxine (fT4), are also known to be genetically influenced. Although observational epidemiological studies report an increased co-occurrence of migraine and thyroid dysfunction, a clear and combined interpretation of the findings is currently lacking. A narrative review is provided of the epidemiological and genetic association evidence linking migraine, hypothyroidism, hyperthyroidism and thyroid hormones TSH and fT4. An extensive literature search was conducted in the PubMed database for epidemiological, candidate gene and genome-wide association studies using the terms migraine, headache, thyroid hormones, TSH, fT4, thyroid function, hypothyroidism and hyperthyroidism. Epidemiological studies suggest a bidirectional relationship between migraine and thyroid dysfunction. However, the nature of the relationship remains unclear, with some studies suggesting migraine increases the risk for thyroid dysfunction whilst other studies suggest the reverse. Early candidate gene studies have provided nominal evidence for MTHFR and APOE, whilst more recently genome-wide association studies have provided robust evidence for THADA and ITPK1 being associated with both migraine and thyroid dysfunction. These genetic associations improve our understanding of the genetic relationship between migraine and thyroid dysfunction, provide an opportunity to develop biomarkers to identify migraine patients most likely to benefit from thyroid hormone therapy, and indicate that further cross-trait genetic studies have excellent potential to provide biological insight into their relationship and inform clinical interventions.

Iodinated Contrast Administration and Risks of Thyroid Dysfunction: A Retrospective Cohort Analysis of the U.S. Veterans Health Administration System.

Background: Iodine-induced thyroid dysfunction is a potential risk among susceptible individuals. Iodinated contrast media is a common source of an acute iodine load used in the health care setting and is frequently required for diagnostic computed tomography scans, coronary angiograms, and other radiologic studies. However, the epidemiologic risks of iodine-thyroid dysfunction have not been fully established in the United States. Methods: This population-based retrospective cohort study used the U.S. Veterans Health Administration database between 1998 and 2021 and included adults aged ≥18 years with a serum thyrotropin (TSH) measurement. Multivariable logistic regression was used to ascertain the risk of incident thyroid dysfunction (defined by repeated measurements of serum thyroid function) following iodine exposure, adjusting for age, sex, race/ethnicity, baseline serum TSH concentration, and duration between baseline and follow-up TSH concentration. Results: The cohort was composed of N = 4,253,119 veterans (mean ± SD = 63.5 ± 14.3 years; 92.9% men; 65.6% non-Hispanic Whites) with 8,729,155 corresponding pairs of serum TSH measurements, from which there were 499,897 TSH pairs with intervening iodine exposure. Thyroid dysfunction occurred in 4.8% of those pairs who had received iodine contrast and 3.6% of those without iodine exposure. Iodinated exposure was associated with an increased risk of thyroid dysfunction (odds ratio [OR] = 1.39, 95% confidence intervals [CI] = 1.37-1.41, p < 0.001) and consistent for all types of serum thyroid dysfunction (overt or subclinical hypo-/hyperthyroidism). Men were at higher risk for the development of thyroid dysfunction than women (men: OR = 1.42, 95% CI = 1.40-1.44; women: OR = 1.16, 95% CI = 1.11-1.21; p-for-interaction <0.001). Conclusions: In this largest analysis of U.S. adults to date, iodine exposure was associated with only clinically small absolute increased risks of thyroid dysfunction, particularly in men. These findings suggest that screening of thyroid function following iodinated contrast administration should be targeted to high-risk individuals.

A community based prospective study on thyroid dysfunction among pregnant females and its effect on maternal and neonatal outcome

Background: Thyroid disorders are often overlooked in pregnancy because of their non-specific symptoms and the hypermetabolic state of pregnancy. The laboratory measurements of thyroid function play an important role in the assessment of maternal thyroid health. Thyroid disorders can have grievous effect on mother and new-borne which can be prevented. The study was aimed to find the prevalence of thyroid dysfunction among pregnant females and its effect on maternal and neonatal outcome.Methods: A prospective study was conducted from August 2019 to October 2020 among 360 pregnant females in the rural fields practice area of a medical college. Thyroid function test was done in all pregnant females and the maternal and neonatal outcome was noted.Results: 20.31% of the pregnant females were found to be suffering from thyroid dysfunction which is approximately 1/5th of the total sample. Out the total females with thyroid dysfunction maximum females suffered from subclinical hypothyroidism that is 10.94% while 1.56% had overt hypothyroidism. 1.88% and 5.94% had subclinical and overt hyperthyroidism respectively. Postpartum haemorrhage, pre term delivery, abortion and neonatal deaths were more common in females with thyroid dysfunction as compared to euthyroid females although not statistically significant.Conclusions: Though pregnancy outcome was not found to be significantly adverse among females with thyroid dysfunction, very high prevalence of thyroid dysfunction among pregnant warrants its detection during antenatal care to be uniformly included in peripheral health care centres.

Relationship between dietary selenium intake and serum thyroid function measures in U.S. adults: Data from NHANES 2007-2012.

Although numerous studies have explored the relationship between selenium intake and thyroid diseases, few epidemiological studies have investigated the association between selenium intake and thyroid hormones. Therefore, we conducted this analysis to investigate the association between dietary selenium intake and thyroid hormones. Our sample included 5,575 adults (age ≥ 20) years from the National Health and Nutrition Examination Survey (NHANES) 2007–2012. Thyroid hormones, including total triiodothyronine (T3), total thyroxine (T4), free T3 (FT3), free T4 (FT4), and thyroid-stimulating hormone (TSH), were detected. Multivariable linear regression models showed that log10-transformed selenium intake (LogSe) was negatively correlated with TT4 (β = −0.383, 95% CI: −0.695, −0.070) and TT4/TT3 (β = −0.003, 95% CI: −0.006, −0.0004) in U.S. adults. Besides, additional stratified analyses by sex demonstrated that LogSe was negatively associated with TT4 (β = −0.007, 95% CI: −0.013, −0.001) and TT4/TT3 (β = −0.664, 95% CI: −1.182, −0.146) and positively associated with FT4/TT4 (β = 0.031, 95% CI: 0.004, 0.059) in male adults. Meanwhile, subgroup analysis by iodine status showed that LogSe was negatively associated with TT4 (β = −0.006, 95% CI: −0.011, −0.002), FT4/FT3 (β = −0.011, 95% CI: −0.023, −0.00002) and TT4/TT3 (β = −0.456, 95% CI: −0.886, −0.026) in iodine sufficiency but not in iodine deficiency adults. Our results demonstrated that the increased dietary selenium intake was negatively correlated with TT4 and TT4/TT3 in U.S. adults. Furthermore, the association between dietary selenium intake and thyroid hormones was more pronounced in males and iodine sufficiency adults.

Laboratory policies and practices for thyroid function tests in Croatia: survey on behalf of Working Group for Laboratory Endocrinology of the Croatian Society of Medical Biochemistry and Laboratory Medicine.

IntroductionLaboratory plays important part in screening, diagnosis, and management of thyroid disorders. The aim of this study was to estimate current laboratory preanalytical, analytical and postanalytical practices and policies in Croatia.Materials and methodsWorking Group for Laboratory Endocrinology of the Croatian Society of Medical Biochemistry and Laboratory Medicine designed a questionnaire with 27 questions and statements regarding practices and protocols in measuring thyroid function tests. The survey was sent to 111 medical biochemistry laboratories participating in external quality assurance scheme for thyroid hormones organized by Croatian Centre for Quality Assessment in Laboratory Medicine. Data is presented as absolute numbers and proportions.ResultsFifty-three participants returned the questionnaire. Response rate varied depending on question, yielding a total survey response rate of 46-48%. All respondents perform thyroid stimulating hormone (TSH). From all other thyroid tests, most performed is free thyroxine (37/53) and least TSH-stimulating immunoglobulin (1/53). Laboratories are using nine different immunoassay methods. One tenth of laboratories is verifying manufacturer’s declared limit of quantification for TSH and one third is verifying implemented reference intervals for all performed tests. Most of laboratories (91%) adopt the manufacturer’s reference interval for adult population. Reference intervals for TSH are reported with different percentiles (90, 95 or 99 percentiles).ConclusionThis survey showed current practices and policies in Croatian laboratories regarding thyroid testing. The results identified some critical spots and will serve as a foundation in creating national guidelines in order to harmonize laboratory procedures in thyroid testing in Croatia.

Exposure to PFAS in two Alaska Native Communities

Background: Many Arctic Indigenous communities are disproportionately exposed to persistent bioaccumulative toxicants due to global distillation and traditional diets. There is relatively little known about sources of exposure to PFAS in Arctic Indigenous Communities. Aim: The aim of this study was to assess exposure to, and health effects of, PFAS in two Arctic Indigenous communities on Sivuqaq (St. Lawrence Island), Alaska. Methods: Working within an established community-based participatory research program we assessed exposure to PFAS using human serum samples, indoor dust, traditional foods, as well as sentinel fish species. Results: Community members on Sivuqaq have broadly similar PFAS exposures to the U.S. population as measured by NHANES; however, select long chain PFAS such as PFNA and PFUNA appear elevated among Sivuqaq residents. Several PFAS are associated with circulating thyroid hormone concentrations in this this population. PFAS are present in traditional food animals as well as sentinel fish species collected in Sivuqaq. Sentinel fish suggest some aspect of the built environment acts as a point source of PFAS. Fish data also suggest strong species level effects in accumulation of PFAS. Dust concentrations of PFAS are on the low end of those reported and suggest the indoor environment may be a comparatively minor contributor to serum PFAS in this population. Discussion: Alaska Native communities are exposed to PFAS through multiple routes of exposure. This may result in elevated exposure for select PFAS. Serum PFAS are associated with measures of thyroid function.

Association Between Serum Vitamin D And TSH Status Levels And Thyroid Stimulating Hormone (TSH) In Postmenopausal Women

Introduction: Vitamin D (VitD) insufficiency is present in over half of population worldwide. Over a billion people worldwide are vitamin D deficient or insufficient. It has been long known that VitD insufficiency contributes to development of osteopenia and osteoporosis. Objective: To assess the serum vitamin D and TSH status in postmenopausal women who have undergone routine blood investigations. Methods: We performed a retrospective review of data of 61 patients in postmenopausal age group (45-75yrs) during their routine blood investigation for the first time at Dept. of Obstetrics and Gynaecology, Shaheed Tajuddin Ahmad Medical College Hospital, Gazipur, Bangladesh from January to March 2021. The data was collected from medical record section and appropriate statistical analysis was done using percentage and frequency. Results: Out of 61 patients Vitamin D was insufficient (10-30 ng/mL) in 34.4% and deficient (&lt;10 ng/mL) in 18.0%, and remaining normal. In 4.9%, TSH was low (less than 0.3 mIU/L) and in 18.0% TSH was high (more than 4.5 mIU/L), while the remaining 77.0 had normal TSH levels (0.3-4.5 mIU/L). 54.5%(n-11) patients with high TSH, had vitamin D deficiency and 18% patients with high TSH had insufficient vitamin D. 100% (n-3) of patients with low TSH had normal vitamin D. 22 patients had normal TSH and normal vitamin D. Conclusion: Prospective longitudinal studies with larger subject numbers and more comprehensive measurement of thyroid function along with examining the indicators of innate immunity may shed light into the underlying pathophysiology and mechanisms involved in the interaction between thyroid function and VitD metabolism. High TSH levels was associated with low vitamin D levels, low TSH levels was associated with normal serum vitamin D level. Hence association was linear between TSH and vitamin D in post-menopausal women.

The effect of obesity-related allostatic changes on cardio-metabolic risk in euthyroid children.

The hormonal thyroid changes related to obesity, even when in the euthyroid state, may contribute to the unfavorable cardio-metabolic profile of obese patients. In this retrospective study, we aim to investigate the biochemical thyroid changes and the association between serum TSH, FT4, FT3 and cardio-metabolic risk factors in euthyroid obese youths. Four hundred ninety-one Caucasian euthyroid obese children and adolescents aged 9.93 ± 2.90years were recruited. Each patient underwent clinical and auxological examination and laboratory workup including an OGTT and the measurement of thyroid function and lipid profile. Homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride to high-density lipoprotein cholesterol ratio, total cholesterol to HDL ratio, atherogenic index of plasma, insulinogenic index, area under the glucose and insulin curves were calculated. We found that TSH was positively correlated with BMI-SDS values and significantly associated with hypercholesterolemia and hyperinsulinemia; FT4 resulted negatively correlated with BMI-SDS; FT3 was positively correlated with BMI-SDS and the area under the curve of insulin and negatively correlated with HDL. FT3 and FT4 resulted significantly associated with severe obesity. In addition, children with high-normal TSH values showed higher triglyceride to high-density lipoprotein cholesterol ratio values than those with normal TSH levels. Our data showed that thyroid hormones could influence obesity, lipid and glycemic parameters in euthyroid youths. These findings could carry implications regarding optimal TSH levels in obese children and confirm the importance of evaluating the thyroid function as possible adjunctive cardio-metabolic risk factor related to obesity.

FT3/FT4 ratio is correlated with all-cause mortality, cardiovascular mortality, and cardiovascular disease risk: NHANES 2007-2012.

BackgroundThyroid hormones play a vital role in maintaining the homeostasis of the cardiovascular system. The FT3/FT4 ratio can be used to evaluate the rate of T4-to-T3 conversion, reflecting the peripheral sensitivity of thyroid hormones. There is no study to investigate its relationship with death and cardiovascular disease (CVD) in the general population.MethodsThis retrospective cohort study involved 8,018 participants with measured thyroid function and no prior thyroid disease who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. Mortality status was determined by routine follow-up using the National Death Index through December 31, 2015.ResultsDuring a median of 87 months of follow-up, we observed 699 all-cause deaths, including 116 cardiovascular deaths. In multivariate adjusted models, higher free thyroxine (FT4) was linked to increased all-cause mortality (HR, 1.15 per SD; 95% CI, 1.09-1.22), cardiovascular mortality (HR, 1.18 per SD; 95% CI, 1.01-1.39), and CVD risk (HR, 1.17 per SD; 95% CI, 1.08-1.27). Higher free triiodothyronine (FT3) was linked to decreased all-cause mortality (HR 0.81 per SD; 95% CI, 0.70-0.93). Higher FT3/FT4 ratio was linked to decreased all-cause mortality (HR, 0.77 per SD; 95% CI, 0.69-0.85), cardiovascular mortality (HR, 0.79 per SD; 95% CI, 0.62-1.00), and CVD risk (HR, 0.82 per SD; 95% CI, 0.74-0.92). The FT3/FT4 ratio stratified findings were broadly consistent with the overall results.ConclusionsFT3, FT4, and the FT3/FT4 ratio were all independent predictors of all-cause death. FT4 and the FT3/FT4 ratio, but not FT3, were independent predictors of cardiovascular mortality and CVD risk. Along with FT3 and FT4, we should pay equal attention to the FT3/FT4 ratio in the general population.

Prediction of recurrent spontaneous abortion using evolutionary machine learning with joint self-adaptive sime mould algorithm

Recurrent spontaneous abortion (RSA) is a frequent abnormal pregnancy with long-term psychological repercussions that disrupt the peace of the whole family. In the diagnosis and treatment of RSA worsened by thyroid disorders, recurrent spontaneous abortion is also a significant obstacle. The pathogenesis and possible treatment methods for RSA are yet unclear. Using clinical information, vitamin D and thyroid function measurements from normal pregnant women with RSA, we attempt to build a framework for conducting an effective analysis for RSA in this research. The framework is presented by combining the joint self-adaptive sime mould algorithm (JASMA) with the common kernel learning support vector machine with maximum-margin hyperplane theory, abbreviated as JASMA-SVM. The JASMA has a complete set of adaptive parameter change methods, which improves the algorithm’s global search and optimization capabilities and guarantees that it speeds convergence and departs from the local optimum. On CEC 2014 benchmarks, the property of JASMA is validated, and then it is utilized to concurrently optimize parameters and select optimal features for SVM on RSA data from VitD, thyroid hormone levels, and thyroid autoantibodies. The statistical results demonstrate that the proposed JASMA-SVM can be treated as a potential tool for RSA with accuracy of 92.998%, MCC of 0.92425, sensitivity of 93.286%, specificity of 93.064%.

ASSESSMENT OF THYROID HORMONE ABNORMALITIES IN PATIENTS OF DOWN SYNDROME

Down syndrome is the fourth most come syndrome caused by chromosomal abnormalities. This syndrome includes many abnormalities such as thyroid hormone disfunction. The current study was designed to determine the prevalence of thyroid dysfunction in clinically diagnosed cases of Down syndrome patients that were confirmed on karyotyping later before including in the study. This Cross-sectional study was carried out at different Hospitals of Lahore to find out the prevalence of thyroid hormone dysfunction in 50 clinically diagnosed Down syndrome (DS) subjects from September 2019 to May 2021 by measuring thyroid function test (T3, T4, TSH), and antithyroid antibodies (ATA). A total 50 Down syndrome cases were included in the study and found majority of the patients were males 33(66.0%) while 17(34.0%) were female. Thyroid dysfunction was found in 27 (54%) of DS subjects, of whom 13 (26.0%) had hypothyroidism, 08 (16.0%) were having subclinical hypothyroidism, 01 (2.0%) had sick thyroid syndrome, 4 (8.0%) were hyperthyroidism and 01 (2.0%) were subclinical hyperthyroidism. ATA was positive in 07 (14.0%) patients of DS, of whom 02 (28%) were male and 05 were female (72%), 03 had hypothyroidism, 02 had hyperthyroidism, 02 had subclinical hypothyroidism. remaining 23 (46.0%) were having euthyroid status. This study showed 54% of down syndrome patients that were clinically diagnosed had thyroid hormone dysfunction. It can be concluded that thyroid hormone dysfunction in found in high prevalence in DS patients.

The Association Between Circulating Trans Fatty Acids and Thyroid Function Measures in U.S. Adults.

BackgroundThere has been controversial evidence regarding the effect of trans fatty acids (TFAs) on thyroid function in animal studies, and the epidemiological studies are lacking. We aimed to investigate the potential associations between circulating TFAs and thyroid function biomarkers in a U.S. adult population sample.MethodsWe performed a cross-sectional survey with 626 adults aged ≥20 years who participated in the National Health and Nutrition Examination Survey (NHANES) 2009–2010. Multivariable linear regression models were constructed to elucidate the relationships between circulating concentrations of TFAs (palmitelaidic acid, vaccenic acid, elaidic acid, linoelaidic acid and the sum of the four TFAs) and a panel of thyroid function measures.ResultsFor 626 adults, positive associations were found between palmitelaidic acid, elaidic acid and total thyroxine (TT4), between palmitelaidic acid and total triiodothyronine (TT3), and between linolelaidic acid and thyroid stimulating hormone (TSH), while linolelaidic acid was negatively associated with free thyroxine (FT4) (all P<0.05). Besides, the four TFAs and the sum TFAs were positively associated with free triiodothyronine (FT3). Vaccenic acid, elaidic acid, linoelaidic acid and the sum TFAs were positively associated with FT3/FT4, while the four TFAs and the sum TFAs were negatively associated with FT4/TT4 (all P<0.05). In stratified analysis, the associations between thyroid function measures and the ratios remained significant in female. For men, linolelaidic acid was negatively associated with FT4 and elaidic acid and the sum TFAs were positively associated with FT3. Furthermore, the associations between TFAs and FT3/FT4 remained significant.ConclusionOur findings revealed that TFAs exposure was associated with serum biomarkers of thyroid function. More researches are needed to evaluate the long-term health outcomes of these findings.

P-732 Definitions and diagnostic criteria for unexplained infertility (UI) – a systematic review

Abstract Study question What are the various inclusion criteria for the definition of unexplained infertility used for recruitment to clinical trials, and is there homogeneity of these definitions? Summary answer There is a need to standardise the definition of unexplained infertility when recruiting for clinical trials to optimise interpretation of results and allow appropriate meta-analysis. What is known already Unexplained infertility (UI) is a diagnosis of exclusion. The pathology underlying this diagnosis is likely to include different subtle contributing factors. Unfortunately there is no universally accepted definition of unexplained infertility. NICE in the UK, and ACOG/ASRM both have lists of recommended investigations but no specific minimum standards to define UI. Even the ICMART definition is ambiguous, describing ‘apparently normal’ ovarian function and ejaculate. This may lead to heterogeneity between inclusion criteria in relevant research studies. This introduces selection bias and renders meta-analysis of trial results less meaningful. A single definition would improve the quality of research for this important diagnosis. Study design, size, duration A systematic review of primary research investigating definitions of unexplained infertility in humans. A thorough search of online databases Medline and Embase was performed from inception to November 2021. A bespoke Excel spreadsheet was used to collect data for baseline study characteristics and outcome data. Results are reported as percentages. Participants/materials, setting, methods The search strategy included all primary research on heterosexual couple unexplained infertility in human participants. Papers with specified inclusion criteria were included and no date or language restrictions were applied. From 663 results, title and abstract screening identified 83 duplicates and 6 studies unsuitable for the review. A further 275 papers were excluded after full-text screening. 241 papers remained and their inclusion criteria recorded and analysed. Main results and the role of chance Only 35.7% of papers specified duration of infertility. Timescales varied from 1 year (46.5%), 2 years (39.5%) or 3 years (14%). 85% papers specified that semen analysis should be ‘normal’. Of these, 40% used the most recent WHO criteria. No other national or international criteria for grading semen analysis was identified. 90% studies required fallopian tube patency as an inclusion criteria. Of these, 65.4% specified bilateral patency. Methods for demonstrating patency included hysterosalpingogram (HSG) (15.7%), laparoscopy (18.4%), a combination of either (29.5%) or both (24.4%) of these or hystero-contrast-salpingography (0.9%). 11.5% papers did not specify an imaging modality. 48.5% included studies mentioned uterine cavity assessment, 65% of these using HSG to assess the cavity, other methods mentioned include ultrasound (26.5%) or hysteroscopy (15.4%). Only 5.4% papers required either exclusion of or evidence of only minimal endometriosis 80.5% of included papers required evidence of regular ovulation. 58.7% used luteal serum progesterone levels, 41.2% required regular cycles (patient-reported) and 17.5% used basal body temperature pattern assessment. Other methods mentioned by a minority of papers include endometrial biopsy, ultrasound follicular tracking, serum and urinary luteinising hormone levels. 44% studies required normal endocrine profiles of which 66% measured prolactin and FSH and 50% measured thyroid function. Limitations, reasons for caution The strength of this study is that we included all primary research papers studying unexplained infertility with no time limitations. Included studies originated from across the world. This is a thorough representation of criteria used across all clinical trials for unexplained infertility. Wider implications of the findings Only 63/241 (26%) studies included duration of infertility, tubal patency, proof of ovulation and semen analysis in their inclusion criteria. This demonstrates the need for standardisation of the definition of unexplained infertility. If future research can apply the same inclusion criteria this will reduce selection bias and allow appropriate meta-analysis. Trial registration number NA

Evaluation of the AFIAS-1 thyroid-stimulating hormone point of care test and comparison with laboratory-based devices.

Thyroid-stimulating hormone (TSH) is the routine primary screening test to assess thyroid function and rapid measurement of TSH levels is highly desirable especially in emergency situations. In the present study, we compared the analytical performance of a commercially available point-of-care test (AFIAS-1) and five laboratory-based systems. Left over material of 60 patient plasma samples was collected from patient care and used in the respective assay. For statistical analysis of the produced data Bland-Altman and Passing-Bablok regression analysis were applied. Good correlation (r=0.982 or higher) was found between all devices. Slopes from regression analysis ranged from 0.972 (95% CI: 0.927-1.013) to 1.276 (95% CI: 1.210-1.315). Among the compared devices, imprecision was high in terms of coefficient of variation (CV=10.3%) for low TSH concentrations and lower (CV=7.3%) for high TSH concentrations. Independent of the method used, we demonstrated a poor standardization of TSH assays, which might impact clinical diagnosis e.g. of hyperthyreosis. This study shows that the point-of-care (POC) test AFIAS-1 can serve as an alternative to laboratory-based assays. In addition the data imply that better standardization of TSH measurements is needed.

Evaluation of peripheral olfactory pathways in chronic autoimmune thyroiditis.

In this study, we aimed to radiologically evaluate the olfactory bulb (OB) volume and olfactory sulcus (OS) depth of adult patients diagnosed with chronic autoimmune thyroiditis. Sixty-eight patients over 18years of age with Hashimoto's thyroiditis and 66 healthy controls with normal thyroid function tests were included in the study. OB volume and OS depth measurements were performed using cranial magnetic resonance imaging (MRI) obtained from coronal T2-weighted images. The relationship between thyroid function tests, autoantibodies, and measurements of the OB and OS were evaluated. The right and left OB volumes were significantly lower in the patients with Hashimoto's thyroiditis than in the control group (p < 0.05). No significant difference was found between the patient and control groups in terms of OS depth (p > 0.05). There were significantly negative correlations among TSH, thyroid antibodies, and the bilateral OB volume measurements. In the Bonferroni post hoc analysis, when people with euthyroid Hashimoto's thyroiditis and the control group were compared, there was no statistically significant difference between bilateral OB volumes and thyroid function tests. Diminished bilateral OB volumes were found in our patients with chronic autoimmune thyroiditis. Interestingly, the OB volumes were not affected in patients with euthyroid Hashimoto's thyroiditis. When a decrease in OB volume is detected on MRI, it should be kept in mind that odor dysfunction in hypothyroid patients with Hashimoto's thyroiditis may occur and patients should be clinically evaluated.

Genetic, clinical, and biochemical aspects of patients with Alzheimer disease

BackgroundThe most common form of dementia is Alzheimer’s disease (AD). The clinical manifestations of AD are loss of memory that is progressive and deterioration in cognitive function. The objective of this study is to find patterns of AD among patients regarding clinical aspects, psychological aspects, and laboratory aspects, as well as to determine the role of some genes (APOE1, APOE2, and TMEM106B) in the pathogenesis of AD. In this case–control study, 40 patients with AD were recruited from the inpatient neurology departments and outpatient neurology clinics of the university hospitals in the period of January 1 to December 31, 2017. Furthermore, 40 cross-matched control patients underwent a complete history taking, neurological examination, brain MRI or CT, psychometric tests, thyroid function, and lipid profile measurements. Extracted DNA was quantified using a nanodrop analyzer (ND-1OOO) spectrophotometer for TMEM106B (rs1990622), APOE2 (rs429358), and APOE1 (rs7412).ResultsAll subtypes of lipid profiles were significantly higher in patients with AD than the controls. There was a significant difference between the two groups regarding TMEM106B. There was an insignificant difference regarding thyroid hormones T3, T4, and TSH between patients and controls. There was no significant difference between AD patients and the control group regarding APOE-1 and APOE-2. Patients were worse than controls in tests of cognition, such as The Cognitive Abilities Screening Instrument (CASI) and auditory number and letter span test. In addition, AD patients had more depression than controls.ConclusionThere may be a significant role of a high lipid profile and TMEM106B expression in the pathogenesis of AD.

Immunological Microenvironment Alterations in Follicles of Patients With Autoimmune Thyroiditis.

Autoimmune thyroiditis (AIT) is the most prevalent autoimmune endocrine disease, with a higher incidence in women than in men. Immunological abnormalities may lead to the impairment of ovarian folliculogenesis; however, whether the presence of AIT affects immunological microenvironment in follicles remains controversial. We performed a cross-sectional study including 122 patients, aged 20–40 years, who underwent IVF/ICSI treatment owing to isolated male or tube factor infertility. Patients were divided into AIT and control groups according to clinical presentation, thyroid function, and thyroid autoantibody measurements. Follicular fluid was collected and the distribution of cytokines/chemokines in follicular fluid was measured by flow cytometry using multiplex bead assays between the two groups. Based on differences in levels of intrafollicular chemokines and cytokines between the AIT and control groups, the relevant inflammatory cascade was further demonstrated. Among the 12 chemokines analyzed, three (CXCL9, CXCL10, and CXCL11) showed significantly elevated levels in the follicular fluid of patients with AIT. Among the 11 cytokines detected, compared with those in the control group, significantly higher levels of IFNγ were observed in patients with AIT. IFNγ dose-dependently stimulated the expression and secretion of CXCL9/10/11 in cultured primary granulosa cells. The percentage of CXCR3+ T lymphocytes was significantly elevated in the follicular microenvironment of patients with AIT. We concluded that the IFNγ-CXCL9/10/11-CXCR3+ T lymphocyte inflammatory cascade is activated in the follicular microenvironment of patients with AIT. These findings indicate that a considerable immune imbalance occurred in the follicular microenvironment of patients with AIT.

Altered Thyroid Function Tests Observed in Hypophosphatasia Patients Treated with Asfotase Alfa.

Background Asfotase alfa is the only approved treatment that can normalize mineralization in patients with hypophosphatasia (HPP). Its interference in alkaline phosphatase (ALP) dependent immunoassays has been reported. Objective To describe thyroid function tests interfered with by asfotase alfa and elucidate the underlying mechanism. Patients and Methods. Three patients with HPP treated with asfotase alfa were included. Thyroid hormone levels measured using five different immunoassays with or without ALP as a labeling enzyme during asfotase alfa treatment were evaluated. Results After the initiation of asfotase alfa, three HPP patients showed low free triiodothyronine (FT3) and free thyroxine (FT4) measured with AIA-2000 (Tosoh, Tokyo, Japan), an enzyme immunoassay system that uses ALP as a labeling enzyme, but their thyroid-stimulating hormone (TSH) levels were within the normal range. The other CLEIA system using ALP as a label, AIA-CL2400 (Tosoh, Tokyo, Japan), and ALP-independent immunoassay systems demonstrated normal FT3 and FT4 levels. These data suggested that although the thyroid function of these three patients was normal, asfotase alfa interfered with the thyroid hormone measurements made with AIA-2000. AIA-2000 and AIA-CL2400 adopted one-step and delayed one-step measurements, respectively, and the same antibody was used for both immunoassays. However, asfotase alfa may be absorbed on the magnetic beads used in the AIA reagent with the AIA-2000 system but not absorbed on the microparticles used in AIA-CL2400. Conclusion Clinicians should be aware of the possible interference in thyroid function measurements by adopting specific types of immunoassays in asfotase alfa-treated HPP patients.